Publications by authors named "Pietro Ruggieri"

189 Publications

The Orthopedic-Vascular Multidisciplinary Approach Improves Patient Safety in Surgery for Musculoskeletal Tumors: A Large-Volume Center Experience.

J Pers Med 2021 May 24;11(6). Epub 2021 May 24.

Department of Orthopedics and Orthopedic Oncology, University of Padua, Via Giustiniani, 235128 Padova, Italy.

Wide-margin resection is mandatory for malignant bone and soft tissue tumors. However, this increases the complexity of resections, especially when vessels are involved. Patients in this high-risk clinical setting could be surgically treated using the multidisciplinary orthopedic-vascular approach. This study was carried out in this healthcare organization to evaluate patient safety in term of oncologic outcomes and reduction of the complication rate. We retrospectively reviewed 74 patients (37 males, 37 females; mean age 46 years, range 9-88) who underwent surgical excision for bone/soft tissue malignant tumors closely attached to vascular structures from October 2015 to February 2019. Vascular surgery consisted of isolation of at least one vessel (64 patients), bypass reconstruction (9 patients), and end-to-end anastomosis (1 patient). Mean follow-up was 27 months. Patients' demographics, tumor characteristics, adjuvant treatments, type of orthopedic and vascular procedures, and oncologic and functional outcomes and complications were recorded. Overall survival was 85% at 3 years follow-up. In total, 22 patients experienced at least one major complication requiring further surgery and 13 patients experienced at least one minor complication, whereas 17 reported deviations from the normal postoperative course without the need for pharmacological or interventional treatment. Major complications were higher in pelvic resections compared to limb-salvage procedures ( = 0.0564) and when surgical time was more than 4 h ( = 0.0364) at univariate analysis, whereas the most important multivariate independent predictors for major complications were pelvic resection ( = 0.0196) and preoperative radiotherapy ( = 0.0426). A multidisciplinary ortho-vascular approach for resection of malignant bone and soft tissue tumors tightly attached to important vascular structures should be considered a good clinical practice for patient safety.
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http://dx.doi.org/10.3390/jpm11060462DOI Listing
May 2021

Age-Dependent Remodeling in Infrapatellar Fat Pad Adipocytes and Extracellular Matrix: A Comparative Study.

Front Med (Lausanne) 2021 10;8:661403. Epub 2021 May 10.

Department of Neuroscience, Institute of Human Anatomy, University of Padova, Padova, Italy.

The infrapatellar fat pad (IFP) is actively involved in knee osteoarthritis (OA). However, a proper description of which developmental modifications occur in the IFP along with age and in absence of joint pathological conditions, is required to adequately describe its actual contribution in OA pathophysiology. Here, two IFP sources were compared: (a) IFP from healthy young patients undergoing anterior-cruciate ligament (ACL) reconstruction for ACL rupture ( = 24); (b) IFP from elderly cadaver donors ( = 23). After histopathological score assignment to confirm the absence of inflammatory features (i.e., inflammatory infiltrate and increased vascularity), the adipocytes morphology was determined; moreover, extracellular matrix proteins were studied through histology and Second Harmonic Generation approach, to determine collagens content and orientation by Fast Fourier Transform and OrientationJ. The two groups were matched for body mass index. No inflammatory signs were observed, while higher area, perimeter, and equivalent diameter and volume were detected for the adipocytes in the elderly group. Collagen III displayed higher values in the young group and a lower total collagen deposition with aging was identified. However, collagen I/III ratio and the global architecture of the samples were not affected. A higher content in elastic fibers was observed around the adipocytes for the ACL-IFPs and in the septa cadaver donor-IFPs, respectively. Age affects the characteristics of the IFP tissue also in absence of a pathological condition. Variable mechanical stimulation, depending on age-related different mobility, could be speculated to exert a role in tissue remodeling.
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http://dx.doi.org/10.3389/fmed.2021.661403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141643PMC
May 2021

Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study.

Eur J Cancer 2021 Jul 11;151:150-158. Epub 2021 May 11.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy.

Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study.

Materials And Methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models.

Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles.

Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
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http://dx.doi.org/10.1016/j.ejca.2021.04.017DOI Listing
July 2021

Intraosseous lipoma of the patella: a case report and review of the literature.

Acta Biomed 2021 04 30;92(S1):e2021084. Epub 2021 Apr 30.

University of Padova.

An intraosseous lipoma is considered one of the rarest primary bone tumors. The etiology of this lesion remains unclear; many lesions are asymptomatic and appear only as incidental findings during routine radiographic evaluations. Magnetic resonance imaging of intraosseous lipomas can help to establish a diagnosis and to stage the neoplasm. This is a case report of a 53-year old man with a rare intraosseous lipoma of the patella.
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http://dx.doi.org/10.23750/abm.v92iS1.8519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142750PMC
April 2021

In Vitro Effects of Low Doses of β-Caryophyllene, Ascorbic Acid and d-Glucosamine on Human Chondrocyte Viability and Inflammation.

Pharmaceuticals (Basel) 2021 Mar 23;14(3). Epub 2021 Mar 23.

Department of Molecular Medicine, Histology Unit, University of Padova, 35121 Padova, Italy.

β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary human chondrocytes. Changes in cell viability, intracellular ROS generation, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan were analyzed in primary human chondrocytes exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN. The CM-induced chondrocyte cytotoxicity was reduced by the presence of low doses of BCP alone or in combination with AA and GlcN. The exposure of cells to CM significantly increased κ1 and expression, but when BCP was added to the inflamed cells, alone or in combination with AA and GlcN, gene transcription for all these molecules was restored to near baseline values. Moreover, chondrocytes increased the expression of and when stimulated with AA and GlcN alone or in combination with BCP. This study showed the synergistic anti-inflammatory and antioxidative effects of BCP, AA and GlcN at low doses on human chondrocyte cultures treated with the CM of activated U937 cells. Moreover, the combination of the three molecules was able to promote the expression of and . All together, these data could suggest that BCP, AA and GlcN exert a chondro-protective action.
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http://dx.doi.org/10.3390/ph14030286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005039PMC
March 2021

Rhabdomyosarcoma Cells Produce Their Own Extracellular Matrix With Minimal Involvement of Cancer-Associated Fibroblasts: A Preliminary Study.

Front Oncol 2020 29;10:600980. Epub 2021 Jan 29.

Stem Cells and Regenerative Medicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy.

Background: The interplay between neoplastic cells and surrounding extracellular matrix (ECM) is one of the determinant elements for cancer growth. The remodeling of the ECM by cancer-associated fibroblasts (CAFs) shapes tumor microenvironment by depositing and digesting ECM proteins, hence promoting tumor growth and invasion. While for epithelial tumors CAFs are well characterized, little is known about the stroma composition of mesenchymal cancers, such as in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma during childhood and adolescence. The aim of this work is to identify the importance of CAFs in specifying RMS microenvironment and the role of these stromal cells in RMS growth.

Methods: We assessed in two dimensional (2D) and three dimensional (3D) systems the attraction between RMS cells and fibroblasts using epithelial colon cancer cell line as control. CAFs were studied in a xenogeneic mouse model of both tumor types and characterized in terms of fibroblast activation protein (FAP), mouse PDGFR expression, metalloproteases activation, and ECM gene and protein expression profiling.

Results: In 2D model, the rate of interaction between stromal and malignant cells was significantly lower in RMS with respect to colon cancer. Particularly, in 3D system, RMS spheroids tended to dismantle the compact aggregate when grown on the layer of stromal cells. , despite the well-formed tumor mass, murine CAFs were found in low percentage in RMS xenogeneic samples.

Conclusions: Our findings support the evidence that, differently from epithelial cancers, RMS cells are directly involved in their own ECM remodeling, and less dependent on CAFs support for cancer cell growth.
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http://dx.doi.org/10.3389/fonc.2020.600980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878542PMC
January 2021

Double fractures of the femur: a review of 16 patients.

Eur J Orthop Surg Traumatol 2021 Jan 26. Epub 2021 Jan 26.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy.

Background: Double ipsilateral femoral fractures account for 1-9% of femoral fractures. There is no clear advantage between single or double implant osteosynthesis. We present a series of patients with double ipsilateral femoral fractures, to address the challenges in treatment, namely the implants for osteosynthesis and complications of treatment.

Materials And Methods: We retrospectively studied 16 patients (7 men, 9 women; mean age, 51 years) treated from January 2015 to December 2018. Motor vehicle accidents were the leading cause of injury. Types of fractures were pertrochanteric and shaft (6), pertrochanteric and distal (2), double shaft (3), neck and shaft (2), neck and distal (1), shaft and distal (1), and triple fracture including a pertrochanteric, shaft and distal (1). In five patients, two different implants were used (plate and screws, cannulated hip screws, femoral nail), whereas in 11 patients a long femoral nail was used.

Results: Fourteen patients experienced union at a mean of 3 months (2-6 months). Two patients experienced nonunion: both had plate and screws osteosynthesis. One patient died 15 days after admission from polytrauma and another patient experienced central venous catheter thrombosis and pneumonia. Surgical complications (2 patients) included a thigh skin necrosis, and external fixator pin tract infection/infected non-union. Weight-bearing was delayed in all patients; full weight-bearing was allowed in 11 patients at 4 months postoperatively, and in four patients at 5 months.

Conclusion: Due to the rarity and the difficulty of standardization of double ipsilateral femoral fractures, there is variable information on the optimal osteosynthesis of the fractures and the outcome of the patients. It seems that closed reduction and long hip nailing is the treatment of choice, with few complications.
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http://dx.doi.org/10.1007/s00590-021-02873-wDOI Listing
January 2021

Mid-Term Outcomes after Arthroscopic "Tear Completion Repair" of Partial Thickness Rotator Cuff Tears.

Medicina (Kaunas) 2021 Jan 17;57(1). Epub 2021 Jan 17.

Orthopaedic Clinic, UOC Azienda Ospedaliera of Padova, 35128 Padova, Italy.

: Different arthroscopic procedures are used for partial-thickness rotator cuff tears (PT-RCTs), but there is still no evidence on the superiority of one procedure over the other. The aim of this study was to evaluate the clinical outcomes and the rate of complications of a tear completion repair (TCR) technique. Patients who had undergone arthroscopic TCR technique for PT-RCTs with a follow-up of at least 2-years after surgery were included. The TCR technique involved the removal of the "critical zone" and creating microfractures to biologically support tendon healing. Functional outcomes were assessed prospectively by the Constant score (CS) and active and passive range of movement (ROM). Pain and patient satisfaction were measured using a visual analog scale (VAS). Complication rates were recorded, and tendon integrity was assessed with magnetic resonance imaging (MRI) or ultrasound performed at least 2-years after surgery. Eighty-seven patients with a median age of 57 years were followed-up for a median of 5 years. The CS score improved from 53.5 preoperatively to 94.0 postoperatively ( < 0.001). Median VAS score decreased from 8.6 to 1.0 ( < 0.0001). Median patient satisfaction was 9.3. The overall complication rate was 14.9%. Patients with PT-RCTs of the supraspinatus tendon treated by the TCR technique with "critical zone" removal and biological stimulation by microfractures showed good functional results with excellent strength recovery, a high degree of patient satisfaction, and resolution of painful symptoms at mid-term follow-up.
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http://dx.doi.org/10.3390/medicina57010074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829759PMC
January 2021

Subclavius Tendon Autograft Reconstruction of Traumatic Posterior Dislocation of the Sternoclavicular Joint in Adolescence.

J Long Term Eff Med Implants 2020 ;30(3):161-164

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padova, Italy.

Posterior dislocation of the sternoclavicular joint is a rare and emergent injury. Diagnosis is often missed or delayed. Treatment is challenging because of the joint's inherent instability. This article presents a 15-year-old adolescent who experienced a traumatic posterior dislocation of his right sternoclavicular joint that was treated successfully with open reduction and joint reconstruction using the ipsilateral subclavius tendon autograft. At one-year follow-up, the patient was asymptomatic, with a stable sternoclavicular joint and full range of motion of his right shoulder.
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http://dx.doi.org/10.1615/JLongTermEffMedImplants.2020035922DOI Listing
January 2020

One-Stage Soft Tissue Reconstruction Following Sarcoma Excision: A Personalized Multidisciplinary Approach Called "Orthoplasty".

J Pers Med 2020 Dec 14;10(4). Epub 2020 Dec 14.

Department of Orthopedics and Orthopedic Oncology, University of Padova, 35122 Padova, Italy.

. Wide surgical resection is a relevant factor for local control in sarcomas. Plastic surgery is mandatory in demanding reconstructions. We analyzed patients treated by a multidisciplinary team to evaluate indications and surgical approaches, complications and therapeutic/functional outcomes. . We analyzed 161 patients (86 males (53%), mean age 56 years) from 2006 to 2017. Patients were treated for their primary tumor (120, 75.5%) or after unplanned excision/recurrence (41, 25.5%). Sites included lower limbs (36.6%), upper limbs (19.2%), head/neck (21.1%), trunk (14.9%) and pelvis (8.1%). Orthoplasty has been considered for flaps (54), skin grafts (42), wide excisions (40) and other procedures (25). . At a mean follow-up of 5.3 years (range 2-10.5), patients continuously showed no evidence of disease (NED) in 130 cases (80.7%), were alive with disease (AWD) in 10 cases (6.2%) and were dead with disease (DWD) in 21 cases (13.0%). Overall, 62 patients (38.5%) developed a complication (56 minor (90.3%) and 6 major (9.7%)). Flap loss occurred in 5/48 patients (10.4%). The mean Musculoskeletal Tumor Society (MSTS) and Toronto Extremity Salvage Score (TESS) was 74.8 ± 14 and 79.1 ± 13, respectively. . Orthoplasty is a combined approach effective in management of sarcoma patients, maximizing adequate surgical resection, limb salvaging and functional recovery. One-stage reconstructions are technically feasible and are not associated with increased risk of complications.
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http://dx.doi.org/10.3390/jpm10040278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768416PMC
December 2020

Functional and Radiographic Outcomes of Minimally Invasive Intramedullary Nail Device (MIIND) for Moderate to Severe Hallux Valgus.

Foot Ankle Int 2021 Apr 15;42(4):409-424. Epub 2020 Dec 15.

Orthopaedic, Traumatology and Oncology Clinic, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, Padova, Italy.

Background: This study was aimed at assessing clinical and radiographic outcomes of the Minimally Invasive Intramedullary Nail Device (MIIND) to correct moderate to severe hallux valgus (HV) and the long-term persistence of its effects.

Methods: This case series study involved 100 patients, 84 women and 16 men (mean age, 59 years), who underwent the MIIND procedure with a mean follow-up of 97 months. Assessment was performed preoperatively, postoperatively, at 6 and 12 months, and at last follow-up. Clinical outcomes were evaluated with American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS), and patient satisfaction. Intermetatarsal angle (IMA), metatarsophalangeal hallux valgus angle (HVA), distal metatarsal articular angle (DMAA), and tibial sesamoid position were assessed. Statistical analysis was performed.

Results: The mean AOFAS score improved from 57.9 to 90.5 points, VAS scale was 1.5 ± 2.0, and patients' satisfaction was 8.7 ± 1.4. The mean correction of the HVA and IMA showed a significant correction; however, the effect of time was not statistically significant on DMAA. Sex ( = .047), severity ( = .050), associated procedures ( = .000), and preoperative angle ( = .000) showed significant association with HVA correction and its persistence over time. Age was not statistically significant. Complications were 9 cases of superficial wound infection and 6 recurrences.

Conclusions: The MIIND technique proved a viable procedure to correct moderate to severe HV with a low rate of complications and recurrence, producing significant correction of most radiographic parameters assessed and their persistence, even at long term.

Level Of Evidence: Level IV, case series study.
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http://dx.doi.org/10.1177/1071100720969676DOI Listing
April 2021

Correction to: Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors.

Immun Ageing 2020 Nov 25;17(1):39. Epub 2020 Nov 25.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata, 64, 35128, Padova, Italy.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12979-020-00209-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687751PMC
November 2020

New concepts in the surgical treatment of actual and impending pathological fractures in metastatic disease.

Injury 2020 Nov 11. Epub 2020 Nov 11.

Department of Orthopedics and Orthopedic Oncology, University of Padova, Italy. Electronic address:

Introduction: Long bone metastases are a disease of high social importance. The goals of surgical treatment are to relieve pain, maintain or restore joint function, and prevent or treat pathological fractures. "Oligometastases" is a disease with a limited number (3-5) of metastatic lesions in the same body district, where an aggressive treatment can be carried out with "curative" intent. This study aimed to evaluate patients with bone metastases surgically treated to determine how surgical treatment can influence prognosis and quality of life, comparing solitary metastasis, oligometastases, and multiple metastases.

Patients And Methods: This is a retrospective analysis of 130 patients with long bone metastases surgically treated between October 2015 and August 2019: 40 patients had solitary metastasis; 38 had less than three metastases (oligometastases), and 52 had multiple metastases. Surgery was resection and reconstruction with a cemented prosthesis (95) or nailing (35).

Results: Overall survival was significantly better in patients with solitary metastasis or oligometastases than in those with multiple metastases (p <0.0001). Patients treated with resection and prosthesis had significantly better survival than those treated with nailing (p <0.0001). Implant complications requiring surgical revision occurred in 20 patients treated with prostheses, while no complications occurred in patients treated with nailing.

Discussion: Survival of cancer patients has improved in the last two decades, leading to an increase of diagnosed metastases. Patients with oligometastases have a survival similar to those with a single metastasis. Optimal implants survival curves should stay above the curves of patients survival.

Conclusions: Since there are no differences in survival, patients with oligometastases should be treated as patients with a solitary lesion, with more aggressive surgery (wide resection and reconstruction with prosthesis). Intramedullary nailing is still indicated in metaphyseal or diaphyseal metastases in patients with advanced disease or poor prognosis when the life expectancy does not overcome the expected survival of the nail, avoiding the need for further surgery.
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http://dx.doi.org/10.1016/j.injury.2020.11.025DOI Listing
November 2020

Metal Ion Release, Clinical and Radiological Outcomes in Large Diameter Metal-on-Metal Total Hip Arthroplasty at Long-Term Follow-Up.

Diagnostics (Basel) 2020 Nov 12;10(11). Epub 2020 Nov 12.

Orthopaedic and Traumatologic Clinic, Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.
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http://dx.doi.org/10.3390/diagnostics10110941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698262PMC
November 2020

Midshaft Clavicle Fractures Treated Nonoperatively Using Figure-of-Eight Bandage: Are Fracture Type, Shortening, and Displacement Radiographic Predictors of Failure?

Diagnostics (Basel) 2020 Oct 5;10(10). Epub 2020 Oct 5.

Orthopaedic Clinic, Department of Surgery, Oncology and Gastroenterology DiSCOG, University of Padova, 35128 Padova, Italy.

As there are no clear and unique radiographic predictors of healing disturbances for acute midshaft clavicle fractures, their treatment is still controversial. The aim of the study was to evaluate in midshaft clavicle fractures treated nonoperatively if fracture type (FT), shortening, and displacement, assessed before and after figure-of-eight bandage (F8-B) application, could be considered prognostic factors of delayed union and nonunion. One hundred twenty-two adult patients presenting a closed displaced midshaft clavicle fracture, managed nonoperatively with an F8-B, were enrolled. FT, initial shortening (IS), and initial displacement (ID) were radiographically evaluated at diagnosis, and both residual shortening (RS) and displacement (RD) were measured after F8-B application. The patients were followed up 1, 3, 6, and 12 months post-injury. Multivariate statistical analysis was performed. RD should be considered as radiological predictor of sequelae. Further, an RD equal to 104% of clavicle width was identified as an optimal cut-off point to distinguish between healed and unhealed fractures, and 140% between delayed union and nonunion. Our data pointed out the effectiveness of the F8-B in reducing fracture fragments and restoring clavicular length. In midshaft clavicle fractures of adults, fracture comminution and clavicular shortening did not influence bone healing. On the contrary, RD has been shown as the most likely predictor of both delayed union and nonunion.
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http://dx.doi.org/10.3390/diagnostics10100788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599597PMC
October 2020

Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors.

Immun Ageing 2020 9;17:27. Epub 2020 Sep 9.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata, 64, 35128 Padova, Italy.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis.
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http://dx.doi.org/10.1186/s12979-020-00199-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488050PMC
September 2020

Infrapatellar Fat Pad Gene Expression and Protein Production in Patients with and without Osteoarthritis.

Int J Mol Sci 2020 08 21;21(17). Epub 2020 Aug 21.

Rheumatology Unit, Department of Medicine-DIMED, University-Hospital of Padova, Via Giustiniani, 2, 35128 Padova, Italy.

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.
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http://dx.doi.org/10.3390/ijms21176016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503946PMC
August 2020

Reverse shoulder arthroplasty for treatment of proximal humerus complex fractures in elderly: A single institution experience.

Injury 2020 Jul 26. Epub 2020 Jul 26.

Department of Orthopedics and Orthopedic Oncology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. Electronic address:

Introduction: Treatment of complex proximal humerus fractures (PHFs) in the elderly should provide early mobilization to maintain autonomy and self-care possibility, avoiding further surgery for complications. Nowadays, there is not a gold standard for treatment. Aim of our study was to review our experience with the use of Reverse Total Shoulder Arthroplasty (RTSA) for the treatment of these fractures in the elderly, evaluating complications and functional results.

Materials And Methods: Ninety-one patients older than 65 were treated with RTSA at our Institute between June 2005 and December 2017: there were 14 males and 77 females, with a mean age of 76 years (range 65-87 years). There were 58 fractures (20 Neer 3, 38 Neer 4) and 33 fracture-dislocations (7 Neer 3, 26 Neer 4). Complications were recorded, and functional outcomes were evaluated using the DASH score and Constant score (CS).

Results: Twenty-three complications occurred: 8 cases of scapular notching, 5 neurologic palsies, 4 dislocations, 3 intraoperative diaphyseal fractures, and subclavian artery damage, deep infection, and radiolucent line in one each. No aseptic loosening or breakage was observed. Further surgeries were necessary in 3 cases only, whereas all patients retained their implant at last follow-up. Functional results were satisfactory: mean abduction was 93°, mean flexion was 110°, mean active internal-rotation reached 35°, mean active external-rotation was 25°, mean CS was 54 points and mean DASH score was 45 points.

Discussion: Surgical treatment of complex PHFs should be a "one-shot surgery," especially in the elderly, since further surgeries could compromise patient outcomes and survival. Additional surgery due to complications is less frequent after RTSA than other techniques. A stable reconstruction permitting early mobilization is fundamental in the elderly. Usually, a prolonged immobilization is recommended after ORIF, TSA, and hemiarthroplasty to provide a stable fixation, whereas RTSA allows early mobilization.

Conclusions: In elderly with inadequate bone stock and needing early recovery of autonomy in daily activities, RTSA effectively treats complex PHFs. The incidence of complications requiring revision surgery is low and functional results are satisfactory and predictable.
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http://dx.doi.org/10.1016/j.injury.2020.07.056DOI Listing
July 2020

Minimally Invasive Surgery: Osteotomies for Diabetic Foot Disease.

Foot Ankle Clin 2020 Sep 9;25(3):441-460. Epub 2020 Jul 9.

Department of Surgery, Oncology and Gastroenterology DiSCOG, Orthopedic and Traumatologic Clinic, University of Padova, Via Giustiniani 2, Padova 35128, Italy.

Minimally invasive distal metatarsal diaphyseal osteotomy (DMDO) is an effective procedure for the treatment of complicated chronic diabetic foot ulcers under the heads of all lateral metatarsal bones (including the fifth). Resistant toe ulcers and recurrent pressure ulcers can be treated effectively by DMDO. For diabetic patients, the main advantages of this method are minimal surgical scars and tissue damage, immediately postoperative weight bearing, absence of osteosynthesis and consequent potential infection of metal fixation, reduction of the previous high plantar pressures by the restoration of a harmonic balanced forefoot arch, and rapid ulcer healing.
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http://dx.doi.org/10.1016/j.fcl.2020.05.006DOI Listing
September 2020

Functional outcome and complications after treatment of comminuted tibial fractures or deformities using Ilizarov bone transport: a single-center study at 15- to 30-year follow-up.

Arch Orthop Trauma Surg 2020 Jul 30. Epub 2020 Jul 30.

Department of Surgery, Oncology and Gastroenterology DiSCOG, Orthopaedic, Traumatological and Oncological Clinic, University of Padua, via Giustiniani 2, 35128, Padua, Italy.

Introduction: The aim of this retrospective study was to evaluate long-term outcomes and complications of a single-center and single-surgeon patient series of isolated and comminuted tibial fractures with bone defects or tibial deformities treated by Ilizarov bone transport.

Materials And Methods: Data from a consecutive series of patients with isolated comminuted tibial fractures (Fracture Group: FG) or deformities (Deformity Group: DG) treated between 1987 and 2002 were included. For clinical assessment, the Lower Extremities Functional Scale was used; complications were recorded according to the Dindo classification and statistical analysis was performed.

Results: Overall, 72 patients were enrolled with a mean follow-up of 21.6 years (range 15-30) a mean LEFS of 36.4 (range 0-100). In the FG, the mean LEFS was 21.3 (range 0-98.75), and the external fixation time (EFT) lasted 7.6 months (range 3-18 months) months. In the DG, the mean LEFS was 76.7 (range 55-100), and the EFT was 10.6 months (range 3-20 months). Between the two groups, the clinical evaluation was significantly different, while the EFT was not (p = 0.14). In the FG, the worst results were obtained in the cases of open fractures with a higher percentage of complications and the need for further surgical procedures. The cumulative rate of complications was 55.6% during the first 36 months and 66.7% at the minimum follow-up of 180 months.

Conclusions: Ilizarov bone transport, even at a long follow-up period, proved to be an effective technique for both definitive treatment of comminuted tibial fractures with bone defects or tibial deformities. Although our functional outcomes were lower in patients with exposed fractures, they were in line with the literature, but not influenced by the EFT when properly managed. Most complications occurred during the first 3 years; however, they could also arise much later, even until almost 30 years.
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http://dx.doi.org/10.1007/s00402-020-03562-9DOI Listing
July 2020

A rare case of anterior shoulder dislocation in 1-year- and 10-month-old toddler: case report and literature review.

Arch Orthop Trauma Surg 2021 May 27;141(5):831-835. Epub 2020 Jul 27.

Department of Orthopedics and Orthopedic Oncology, University of Padova, Via N. Giustiniani 2, 35128, Padova, Italy.

We report our clinical experience of a 1 year and 10 month child with traumatic anterior shoulder dislocation who underwent non-operative reduction and Desault's bandage immobilization for 10 days. No associated fractures were found and after bandage removal, full ROM of the shoulder was immediately assessed. Further research is needed to unified guideline of treatment and the time of immobilization for this type of injury in pediatric population.
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http://dx.doi.org/10.1007/s00402-020-03536-xDOI Listing
May 2021

Quality of life outcomes in patients undergoing knee replacement surgery: longitudinal findings from the QPro-Gin study.

BMC Musculoskelet Disord 2020 Jul 4;21(1):436. Epub 2020 Jul 4.

National Research Council, Neuroscience Institute - Aging Branch, via Giustiniani, 2, 35128, Padova, Italy.

Background: Many patients report postoperative pain, limited improvement in physical function and poor quality of life (QOL) after knee replacement surgery. Our study uses baseline predictors of change to investigate the QOL of patients with knee osteoarthritis 3-months after knee replacement surgery.

Methods: A prospective observational study was designed to evaluate patients (n = 132) scheduled for uni-compartmental or total knee replacement surgery who were assessed at baseline (preoperatively) and 3-months after. Physical and mental endpoints based on the component scores of the SF-12 and on the Western Ontario and McMaster Universities Arthritis (WOMAC) index were used to investigate patients' QOL. Generalised estimating equation methodology was used to assess patients' baseline characteristics (age, sex, education, body mass index (BMI), comorbidity, depressive symptoms, cognitive impairment, smoking/alcohol and type of surgery), the study endpoints and their changes over a 3-month post-surgery period. Stratified analyses by rehabilitation status after discharge were performed.

Results: Longitudinal data analysis showed that the baseline factors associated with improvement in general QOL at the 3-month post-surgery assessment were higher BMI, a high comorbidity, total (as opposed to unicompartmental) knee replacement and low education level. Data analysis of the patients who underwent rehabilitation after discharge revealed that the current smokers' physical QOL worsened over time. The general QOL was unchanged over time in the presence of depressive symptomatology.

Conclusions: These findings underline the importance of using comprehensive assessment methods to identify factors affecting functionality and QOL, and developing interventions to improve the health/wellbeing of patients after knee replacement.
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http://dx.doi.org/10.1186/s12891-020-03456-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335448PMC
July 2020

Extraskeletal Myxoid Chondrosarcoma: Clinical and Molecular Characteristics and Outcomes of Patients Treated at Two Institutions.

Front Oncol 2020 16;10:828. Epub 2020 Jun 16.

Medical Oncology 1, Istituto Oncologico Veneto IRCCS, Padova, Italy.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare subtype of STS, which usually arises in extremities. It carries reciprocal translocations involving the NR4A3 gene. It displays an indolent behavior, but studies with long follow-up showed a high proportion of local and distant recurrences. For patients with progressing metastatic disease anthracycline-based chemotherapy is the standard front-line regimen, though has limited activity. There is some evidence on possible activity of antiangiogenetics. This is a retrospective study conducted at Istituto Oncologico Veneto and at Institut Gustave Roussy. All patients with a confirmed diagnosis of EMC from January 1980 to December 2018 were extracted from a prospectively maintained database. 59 patients were identified, 37 male (62.7%) and 22 female (37.3%) with a M/F ratio of 1.7/1. We performed molecular analysis in 23 cases, all carried a EWSR1-NR4A3. Out of 49 patients treated with curative intent, 28.6% developed local recurrence and 40.8% patients developed metastases. In patients who had been radically resected (R0) local recurrence occurred in 7.6% of cases and metastases occurred in 15.4% of cases; in patients treated with R1 surgery, rates of relapse were higher. Twenty patients received chemotherapy for metastatic disease; best response was partial response with clinical benefit in 50% of patients. Fourteen patients received a second line of chemotherapy, with 46.1% disease control rate. A drug holiday was proposed to 8 patients with a mean duration of 22.8 months. Median overall survival was 180 months for the study population and 76 months for metastatic patients. No significant prognostic role was found for all studied variables, yet a trend of better survival for complete surgery, location in extremities of primary tumor and solitary lung metastases was observed. Chemotherapy for metastatic disease was negatively associated with survival. In this large retrospective cohort of patients with ECM, location of primary tumor and solitary lung metastases seem to be associated with better survival. Chemotherapy did not impact survival in unselected patients. Further research is necessary in order to identify more active regimens and to provide clinical and molecular factors to select patients that could delay systemic treatment for metastatic disease.
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http://dx.doi.org/10.3389/fonc.2020.00828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308468PMC
June 2020

The orthopaedic and traumatology scenario during Covid-19 outbreak in Italy: chronicles of a silent war.

Int Orthop 2020 08 26;44(8):1453-1459. Epub 2020 Jun 26.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Padua, PD, Italy.

Background: From February 21, the day of hospitalisation in ICU of the first diagnosed case of Covid-19, the social situation and the hospitals' organisation throughout Italy dramatically changed.

Methods: The CIO (Club Italiano dell'Osteosintesi) is an Italian society devoted to the study of traumatology that counts members spread in public and private hospitals throughout the country. Fifteen members of the CIO, Chairmen of 15 Orthopaedic and Trauma Units of level 1 or 2 trauma centres in Italy, have been involved in the study. They were asked to record data about surgical, outpatients clinics and ER activity from the 23rd of February to the 4th of April 2020. The data collected were compared with the data of the same timeframe of the previous year (2019).

Results: Comparing with last year, overall outpatient activity reduced up to 75%, overall Emergency Room (ER) trauma consultations up to 71%, elective surgical activity reduced up to 100% within two weeks and trauma surgery excluding femoral neck fractures up to 50%. The surgical treatment of femoral neck fractures showed a stable reduction from 15 to 20% without a significant variation during the timeframe.

Conclusions: Covid-19 outbreak showed a tremendous impact on all orthopaedic trauma activities throughout the country except for the surgical treatment of femoral neck fractures, which, although reduced, did not change in percentage within the analysed timeframe.
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http://dx.doi.org/10.1007/s00264-020-04637-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319215PMC
August 2020

Hypermobility of the First Ray: the Cinderella of the measurements conventionally assessed for correction of Hallux Valgus.

Acta Biomed 2020 05 30;91(4-S):47-59. Epub 2020 May 30.

Orthopaedic, Traumatological and Oncological Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, DiSCOG, University of Padova, via Giustiniani 2; 35128 Padova, Italy.

Background And Aim Of The Work: hypermobility of the first ray (FRH) began to be considered as a pathological entity from Morton's studies and was associated as a primary cause of hallux valgus (HV ). Currently, this relationship is in discussion, and various authors consider FRH as a consequence of the deformity. The purpose of this narrative review is to summarise the most influential publications relating to First Ray Mobility (FRM) to increase knowledge and promote its conventional assessment during clinical practice.

Methods: papers of the last century were selected to obtain a homogeneous and up-to-date overview of I-MTCJ mobility and HV, as well as their relationship and management.

Results: in recent years, FRH was studied from a biomechanical and pathophysiologic point of view. There is still not enough data regarding the aetiology of FRM. The higher rate of instability found in HV lacks an explanation of which is the cause and which is the effect. However, the Lapidus arthrodesis is still a valid method in cases of FRH and HV, even if is not rigorously indicated to treat both. When approaching FRH, radiographic or clinical findings are mandatory for the right diagnosis.

Conclusions: FRM is an important factor that must be considered in routine clinical practice and prior and post HV surgery, as much as the conventional parameters assessed. Surgeons should consider performing I-MTCJ arthrodesis only if strictly necessary, also paying attention to soft tissue balancing. Improving the measurement of FRH could be useful to determine if it is a cause or effect of the HV deformity.
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http://dx.doi.org/10.23750/abm.v91i4-S.9769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944838PMC
May 2020

Limb lengthening for deformities in Ollier's disease: a systematic review.

Eur J Orthop Surg Traumatol 2020 Dec 4;30(8):1325-1332. Epub 2020 Jun 4.

Department of Orthopaedics, Division of Surgery, Oncology and Gastroenterology DiSCOG, University of Padua, Padova, Italy.

Background: The management of limb deformity, shortening, and bone defects in treatment of Ollier's disease is a major challenge. This study aims to summarize and compare the different surgical treatments, and to evaluate the outcome and possible prognostic factors of leg lengthening in these patients.

Materials And Methods: A systematic review of the literature from 1993 to 2017 was performed. Nineteen articles were found including a total of 121 patients with limb deformities because of Ollier's disease. The mean patients' age at the time of first surgery was 12 years. A total of 272 segments were surgically treated (14 segments in the upper limbs) with variable techniques including osteotomies and external fixation, intramedullary nails, as well as epiphysiodesis and lengthening over nail. We studied the bone healing index (BHI), distraction index (DI), distraction time, gained length, total treatment time, and complications.

Results: Available implants and techniques allowed correction of patients' deformities (lengthening and correction of angular defects) in most cases. External fixators, circular or monolateral frames were the most commonly used technique. The Ilizarov external fixator was the most commonly used frame (196 segments). The BHI was significantly better when the external fixation was combined with intramedullary nails. Epiphysiodesis was most likely to be more associated with the past than to the present. Joint stiffness, infection, early consolidation, pathological fracture, deformity recurrence, delayed union, non-union, neurapraxia, and overlengthening were the reported complications with an overall rate of 27.9%.

Conclusions: There is no consensus for the optimal surgical technique and implants for correction of limbs deformities in patients with Ollier's disease. External fixators most commonly circular are the most commonly used implants; however, complications do occur.
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http://dx.doi.org/10.1007/s00590-020-02692-5DOI Listing
December 2020

What Is the 10-year Survivorship of Cemented Distal Femoral Endoprostheses for Tumor Reconstructions and What Radiographic Features Are Associated with Survival?

Clin Orthop Relat Res 2020 Nov;478(11):2573-2581

P. Piakong, D. Joyce, D. Letson, O. Binitie, Sarcoma Department, H. Lee Moffitt Cancer and Research Institute, Tampa, Florida, USA.

Background: Aseptic loosening is one of the most common causes of revision of distal femoral endoprostheses and is considered a mid- to long-term complication. There are not many reports of 10-year survivorship free from aseptic loosening and all-cause survivorship in cemented stems. To our knowledge, there are no reports on radiographic features that are associated with aseptic loosening of these implants.

Questions/purposes: (1) What is the 5- and 10-year survivorship free from aseptic loosening in patients undergoing reconstruction with a cemented distal femoral endoprosthesis after a tumor resection? (2) What is the all-cause 5- and 10-year survivorship at in these patients? (3) What radiographic features are associated with aseptic loosening at long-term follow-up?

Methods: We performed a multicenter retrospective study reviewing aseptic loosening in cemented prostheses to determine radiographic features associated with long-term implant survivorship. Patients who underwent a cemented distal femoral reconstruction with a modular endoprosthesis after resection of a musculoskeletal tumor between 1997 and 2017 were reviewed. A total of 246 patients were identified from five institutions and met initial inclusion criteria. Of those, 21% (51) were lost to follow-up before 2 years, leaving 195 patients available for us to evaluate and analyze the survivorship and radiologic features associated with long-term implant survival. The mean (range) follow-up was 78 months (22 to 257). At the time of this analysis, 69% (135 of 195) of the patients were alive. Osteosarcoma was the most common diagnosis in 43% of patients (83 of 195), followed by metastatic carcinoma 13% (25 of 195). Fifty-six percent (110 of 195) of patients received chemotherapy; 15% (30 of 195) had radiation therapy. Aseptic loosening was diagnosed radiographically and was defined as a circumferential radiolucent line on all views, or subsidence around the stem in the absence of infection. We present 5- and 10-year Kaplan-Meier survivorship free from aseptic loosening, 5- and 10-year all-cause survivorship, and a qualitative assessment of radiographic features potentially associated with aseptic loosening (including the junctional radiolucent area, and cortical expansion remodeling). The junctional radiolucent area was defined as a radiolucent area of the bone starting at the bone-endoprosthesis junction to the tip of the femoral stem, and cortical expansion remodeling was defined as an increased cortical thickness at the stem tip. Although we wished to statistically analyze radiographic factors potentially associated with aseptic loosening, we did not have enough clinical material to do so (only nine patients developed loosening). Instead, we will report a few preliminary qualitative observations, which necessarily are preliminary, and which will need to be confirmed or refuted by future studies. We urge caution in interpreting these findings because of the very small numbers involved.

Results: Kaplan-Meier survivorship free from aseptic loosening of the femoral component at 5 and 10 years were 95% (95% CI 89 to 98) and 93% (95% CI 86 to 97), respectively. Kaplan-Meier survivorship free from revision for any cause at 5 and 10 years were 74% (95% CI 65 to 79) and 64% (95% CI 49 to 70), respectively. Although the numbers were too small to analyze statistically, all patients with aseptic loosening had a junctional radiolucent area more than 20% of the total length of the stem without cortical expansion remodeling at the stem tip. No aseptic loosening was observed if there was cortical ex remodeling, a junctional radiolucent area less than 20%, or curved stems that were 13 mm or greater in diameter. The numbers of patients with aseptic loosening in this series were too small to analyze statistically.

Conclusions: Cemented distal femoral endoprostheses have a relatively low rate of aseptic loosening and acceptable projected first-decade survivorship. The presence of a radiolucent area more than 20% without cortical expansion remodeling at the stem tip may lead to aseptic loosening in patients with these implants. Close radiographic surveillance and revision surgery may be considered for progressive lucencies and clinical symptoms of pain. If revision is contemplated, we recommend using larger diameter curved cemented stems. These are preliminary and provisional observations based on a low number of patients with aseptic loosening; future studies with greater numbers of patients are needed to validate or refute these findings.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594923PMC
November 2020

Anti-Inflammatory Performance of Lactose-Modified Chitosan and Hyaluronic Acid Mixtures in an In Vitro Macrophage-Mediated Inflammation Osteoarthritis Model.

Cells 2020 05 26;9(6). Epub 2020 May 26.

Department of Molecular Medicine, Histology Unit, University of Padova, 35121 Padova, Italy.

The development and progression of osteoarthritis (OA) is associated with macrophage-mediated inflammation that generates a broad spectrum of cytokines and reactive oxygen species (ROS). This study investigates the effects of mid-MW hyaluronic acid (HA) in combination with a lactose-modified chitosan (CTL), on pro-inflammatory molecules and metalloproteinases (MMPs) expression, using an in vitro model of macrophage-mediated inflammation.

Methods: To assess chondrocyte response to HA and CTL in the presence of macrophage derived inflammatory mediators, cells were exposed to the conditioned medium (CM) of U937 activated monocytes and changes in cell viability, pro-inflammatory mediators and MMPs expression or ROS generation were analysed.

Results: CTL induced changes in chondrocyte viability that are reduced by the presence of HA. The CM of activated U937 monocytes (macrophages) significantly increased gene expression of pro-inflammatory molecules and MMPs and intracellular ROS generation in human chondrocyte cultures. HA, CTL and their combinations counteracted the oxidative damage and restored gene transcription for IL-1β, TNF-α, Gal-1, MMP-3 and MMP-13 to near baseline values.

Conclusions: This study suggests that HA-CTL mixture attenuated macrophage-induced inflammation, inhibited MMPs expression and exhibited anti-oxidative effects. This evidence provides an initial step toward the development of an early stage OA therapeutic treatment.
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http://dx.doi.org/10.3390/cells9061328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349682PMC
May 2020

Nonmechanical Revision Indications Portend Repeat Limb-Salvage Failure Following Total Femoral Replacement.

J Bone Joint Surg Am 2020 Sep;102(17):1511-1520

Center for Orthopaedic Innovations, Miami, Florida.

Background: There is scant evidence to guide decision-making for patients considering total femoral replacement (TFR). We aimed to identify the indication, patient, disease, and surgical technique-related factors associated with failure. We hypothesized that failure occurs more frequently in the setting of revision surgical procedures, with infection as the predominant failure mode.

Methods: We performed a retrospective cohort study of patients receiving total femoral endoprostheses for oncological and revision arthroplasty indications; 166 patients met these criteria. Our primary independent variable of interest was TFR for a revision indication (arthroplasty or limb salvage); the primary outcome was failure. Analyses were performed for patient variables (age, sex, diagnosis group, indication), implant variables (model, decade, length, materials), and treatment variables. We analyzed TFR failures with respect to patient factors, operative technique, and time to failure. We conducted bivariate logistic regressions predicting failure and used a multivariate model containing variables showing bivariate associations with failure.

Results: Forty-four patients (27%) had treatment failure. Failure occurred in 24 (23%) of 105 primary TFRs and in 20 (33%) of 61 revision TFRs; the difference was not significant (p = 0.134) in bivariate analysis but was significant (p = 0.044) in multivariate analysis. The mean age at the time of TFR was 37 years in the primary group and 51 years in the revision group (p = 0.0006). Of the patients who had mechanical failure, none had reoccurrence of their original failure mode, whereas all 8 patients from the nonmechanical cohort had reoccurrence of the original failure mode; this difference was significant (p = 0.0001).

Conclusions: TFR has a high failure rate and a propensity for deep infection, especially in the setting of revision indications and prior infection. All failed TFRs performed for revision indications for infection or local recurrence failed by reoccurrence of the original failure mode and resulted in amputation.

Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.19.01022DOI Listing
September 2020

Impact of the COVID-19 pandemic on patients suffering from musculoskeletal tumours.

Int Orthop 2020 08 26;44(8):1503-1509. Epub 2020 May 26.

Department of Orthopaedics and Orthopaedic Oncology, University of Padova, Via Nicolò Giustiniani, 3, 35128, Padova, Italy.

Background: The aim of the current study was to evaluate the impact of the coronavirus disease (COVID-19) pandemic on musculoskeletal tumor service by conducting an online survey of physicians.

Methods: The survey was conducted among the members of the ISOLS (International Society of Limb Salvage) and the EMSOS (European Musculo-Skeletal Oncology Society). The survey consisted of 20 questions (single, multiple-response, ranked): origin and surgical experience of the participant (four questions), potential disruption of healthcare (12 questions), and influence of the COVID-19 pandemic on the particular physician (four questions). A matrix with four different response options was created for the particular surgical procedures).

Results: One hundred forty-nine physicians from five continents completed the survey. Of the respondents, 20.1% and 20.7% stated that surgery for life-threatening sarcomas were stopped or delayed, respectively. Even when the malignancy was expected to involve infiltration of a neurovascular bundle or fracture of a bone, still 13.8% and 14.7% of the respondents, respectively, stated that surgery was not performed. In cases of pending fractures of bone tumors, 37.5 to 46.2% of operations were canceled.

Conclusion: The SARS-CoV-2 pandemic caused a significant reduction in healthcare (surgery, radiotherapy, chemotherapy) for malignancies of the musculoskeletal system. Delaying or stopping these treatments is life-threatening or can cause severe morbidity, pain, and loss of function. Although the coronavirus disease causes severe medical complications, serious collateral damage including death due to delayed or untreated sarcomas should be avoided.
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http://dx.doi.org/10.1007/s00264-020-04636-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247966PMC
August 2020